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Topical siRNA therapy of diabetic-like wound healing

E. Neuhoferova, M. Kindermann, M. Buzgo, K. Vocetkova, D. Panek, P. Cigler, V. Benson

. 2025 ; 13 (3) : 1037-1051. [pub] 20250115

Language English Country England, Great Britain

Document type Journal Article

Non-healing wounds are a serious complication in diabetic patients. One of the detrimental factors contributing to limited wound healing is the accumulation of metalloproteinase-9 (MMP-9) in the wound. Selective inhibition of MMP-9 is one of the established therapeutic targets for diabetic wound healing. Here, a functional and biocompatible wound dressing is developed to enable a controlled release of a traceable vector loaded with the antisense siRNA against MMP-9 in the wound. The dressing consists of degradable polymer nanofibers embedded with a vector nanosystem - polymer-coated fluorescent nanodiamonds optimized for the binding of siRNA and colloidal stability of nanodiamond-siRNA complexes in a physiological environment. The developed dressing is tested on murine fibroblasts and also applied to wounds in a diabetic murine model to evaluate its suitability in terms of in vivo toxicity, biological efficacy, and handling. The treatment results in significant local inhibition of MMP-9 and a shortening of the wound healing time. The scar formation in treated diabetic-like mice becomes comparable with that in non-treated diabetes-free mice. Our results suggest that the application of our biocompatible dressing loaded with a non-toxic vector nanosystem is an effective and promising approach to gene therapy of non-healing wounds.

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$a Neuhoferova, Eva $u Institute of Microbiology of the Czech Academy of Sciences, Videnska 1083, 142 20, Prague 4, Czechia. veronika.benson@tul.cz $u Faculty of Science, Charles University, Hlavova 2030, Prague 2, 128 40, Czechia
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$a Non-healing wounds are a serious complication in diabetic patients. One of the detrimental factors contributing to limited wound healing is the accumulation of metalloproteinase-9 (MMP-9) in the wound. Selective inhibition of MMP-9 is one of the established therapeutic targets for diabetic wound healing. Here, a functional and biocompatible wound dressing is developed to enable a controlled release of a traceable vector loaded with the antisense siRNA against MMP-9 in the wound. The dressing consists of degradable polymer nanofibers embedded with a vector nanosystem - polymer-coated fluorescent nanodiamonds optimized for the binding of siRNA and colloidal stability of nanodiamond-siRNA complexes in a physiological environment. The developed dressing is tested on murine fibroblasts and also applied to wounds in a diabetic murine model to evaluate its suitability in terms of in vivo toxicity, biological efficacy, and handling. The treatment results in significant local inhibition of MMP-9 and a shortening of the wound healing time. The scar formation in treated diabetic-like mice becomes comparable with that in non-treated diabetes-free mice. Our results suggest that the application of our biocompatible dressing loaded with a non-toxic vector nanosystem is an effective and promising approach to gene therapy of non-healing wounds.
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$a Kindermann, Marek $u Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo namesti 2, 166 10, Prague 6, Czechia. petr.cigler@uochb.cas.cz $u Department of Physical Chemistry, University of Chemistry and Technology Prague, Technicka 5, 166 28 Prague 6, Czechia $1 https://orcid.org/0009000220747833
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$a Vocetkova, Karolina $u Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 142 20, Prague, Czechia
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$a Panek, Dalibor $u Faculty of Biomedical Engineering, Czech Technical University in Prague, Namesti Sitna 3105, Kladno 2, 272 01, Czechia
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